The esters of steroid acids derived from potent glucocorticoids are being evaluated as safer anti-inflammatory steroids for local use. The local anti-inflammatory activity of these steroid acid esters is equivalent to their parent compounds, but their systemic activity is weaker and, furthermore, they are devoid of systemic side effects. This is in accord with the concept that steroid acid esters with intact ring structures of corticoids possess anti-inflammatory activity per se, but upon entry into the circulatory system from the administration site are hydrolyzed to steroid acids which are inactive and are readily excreted. It is proposed to confirm the findings and validate this concept by pharmacological, biochemical and metabolic studies. New steroid acid esters will be synthesized and comprehensively evaluated as anti-inflammatory agents using the carrageenan-induced rat paw edema, croton oil-induced ear edema test and the cotton pellet granuloma bioassay, with respect to various routes of administration. To further delineate the mode of action of the steroids, their effect on pituitary-adrenal function, glycogen deposition, electrolyte balance, hepatic transaminases, skin collagen synthesis, interaction with various receptor preparations and leukocyte function including migration and liberation of prostanoids, elastase and collagenase will be studied. The metabolic fate of these steroids in rats will also be investigated using radiolabeled compounds. The results of these studies will yield valuable insight into the mode of action of these new classes of corticosteroids with the promise of producing a new series of locally acting anti-inflammatory steroids which are devoid of systemic side effects and thus will be more acceptable for use in the clinical environment.